Adaptation to myocardial stress in disease states: is preconditioning a healthy heart phenomenon?

Effective therapeutic strategies for protecting the ischaemic myocardium are much sought after. Ischaemic heart disease in humans is a complex disorder, often associated with other systemic diseases such as dyslipidaemia, hypertension and diabetes that exert multiple biochemical effects on the heart, independently of ischaemia. Ischaemic preconditioning of myocardium is a well-described adaptive response in which brief exposure to ischaemia markedly enhances the ability of the heart to withstand a subsequent ischaemic insult. The underlying molecular mechanisms of this phenomenon have been extensively investigated in the hope of identifying new rational approaches to therapeutic protection of the ischaemic myocardium. However, most studies have been undertaken in animal models in which ischaemia is imposed in the absence of other disease processes. In this article, Peter Ferdinandy, Zoltan Szilvassy and Gary Baxter review the ways in which systemic diseases might modify the preconditioning response and they emphasize the importance of further preclinical studies that specifically examine preconditioning in relation to complicating disease states.